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Dose-dependent Association (dose-dependent + association)
Selected AbstractsPrevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment studyADDICTION, Issue 6 2009Katinka Anchersen ABSTRACT Aims To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme. Participants and setting Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997,December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT. Design and measures The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross-matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient-years in OMT. Findings In the QTc assessment sample (n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26) had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine (n = 27) had QTc results <450 milliseconds. A positive dose-dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient-years. Only one death among 3850 OMT initiations occurred within the first month of treatment. Conclusion Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient-years. [source] Serum levels of interleukin-10 and tumour necrosis factor- , in chronic periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2010Anna Passoja Passoja A, Puijola I, Knuuttila M, Niemelä O, Karttunen R, Raunio T, Tervonen T. Serum levels of interleukin-10 and tumour necrosis factor- , in chronic periodontitis. J Clin Periodontol 2010; 37: 881,887. doi: 10.1111/j.1600-051X.2010.01602.x Abstract Aims: To investigate, using a cross-sectional study design, whether the extent of periodontal inflammation associates with the serum levels of cytokine interleukin (IL)-10 and tumour necrosis factor (TNF)- , and their ratio. Material and Methods: The study group consisted of 61 subjects with chronic periodontitis and 30 control subjects with minimally inflamed periodontal tissues. Probing pocket depth (PD), bleeding on probing (BOP) and periodontal attachment level (AL) were measured. The serum IL-10 (pg/ml) and TNF- , (U/l) levels were analysed using enzyme-linked immunosorbent assays. After categorization of the subjects, associations between serum IL-10 and TNF- , levels and the extent of periodontal inflammation were studied using linear regression models adjusted for age, gender, body mass index and smoking. Results: A negative, partly dose-dependent association existed between the extent of BOP, PD4 mm and AL4 mm and serum IL-10 level. The subjects in the periodontitis group presented significantly higher serum TNF- , levels and their TNF- ,/IL-10 ratio was approximately threefold when compared with the ratio in the control group. Conclusions: The significantly higher serum TNF- ,/IL-10 ratio in the subjects with chronic periodontitis when compared with the ratio in the controls is indicative of a stronger systemic pro-inflammatory state in chronic periodontitis. [source] The role of paracetamol in the pathogenesis of asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2010H. Farquhar Summary Paracetamol use represents a putative risk factor for the development of asthma. There is convincing epidemiological evidence that the risk of asthma may be increased with exposure to paracetamol in the intrauterine environment, infancy, later childhood and adult life. A dose-dependent association has also been observed in these different age groups in different populations world-wide. An association has also been shown between paracetamol use in both rhinoconjunctivitis and eczema. There is biological plausibility with paracetamol use leading to decreased glutathione levels resulting in increased oxidant-induced inflammation and potentially enhanced T-helper type 2 responses. At the population level, patterns of paracetamol use might explain, to some extent, the world-wide variation in the prevalence of asthma and related disorders, particularly the high rates in English-speaking countries, which have high per capita prescription and over-the-counter use of paracetamol. A temporal association also exists between the international trends of increasing paracetamol use and increasing prevalence of asthma over recent decades. Further research is urgently required, in particular randomized-controlled trials (RCTs) into the long-term effects of frequent paracetamol use in childhood, to determine the magnitude and characteristics of any such risk. Importantly, RCTs will also enable evidence-based guidelines for the recommended use of paracetamol to be developed. Cite this as: H. Farquhar, A. Stewart, E. Mitchell, J. Crane, S. Eyers, M. Weatherall and R. Beasley, Clinical & Experimental Allergy, 2010 (40) 32,41. [source] Determinants of endotoxin levels in living environments of farmers' children and their peers from rural areasCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2004M. Waser Summary Background Lower frequencies of asthma and hayfever have been observed in children with contact to livestock. At school age, the amount of endotoxin measured in the dust of children's mattresses is inversely related to the occurrence of atopic asthma, hayfever and atopic sensitization both in children from farming and non-farming households. Objective The aim of the present study was to investigate which home and lifestyle characteristics of farm and non-farm families contribute to endotoxin levels measured in different indoor home environments. Methods In the framework of the Allergy and Endotoxin (ALEX) Study, endotoxin was measured in dust samples from the living room floor and the child's mattress of 319 farmers' families and 493 non-farming families, and in settled dust from stables. Endotoxin content of all dust samples was determined by a kinetic Limulus assay (Limulus - Amebocyte -Lysate test). Information about the child's activities on farms, home characteristics and cleaning behaviours was obtained from parental questionnaires. Results Endotoxin levels in stables did not predict the amount of endotoxin measured in floors or mattresses. However, a dose-dependent association between the child's activity on the farm and indoor home endotoxin levels was observed, both in farm and non-farm children. In non-farm children pet keeping and the frequency of floor cleaning were additionally associated with endotoxin levels, whereas in farm children parental farm activities, study area, time since last cleaning, the mattress type as well as younger age of the children contributed to increased microbial exposure. Conclusion These results demonstrate that regular contact to farm animals increases indoor home endotoxin concentrations, both in farm and non-farm children, and might thus explain the protective effect of contact to livestock on atopic outcomes. To assess children's individual exposure to a microbial environment, measures of mattress dust exposure are needed as stable endotoxin concentrations were not associated with indoor home levels. [source] | ||||||||||